This application for a Skin Diseases Research Center Grant (SDRC) requests support to create a focus of excellence in cutaneous biology at the Columbia-Presbyterian Medical Center (CPMC) that will maximize the strength within the Department of Dermatology and harness it to the rich opportunities for collaborative research with talented investigators across this campus. The theme of this project is the genetic basis of skin diseases and it is planned to pursue this with the assistance of four Core facilities designed to provide investigators with state-of- the-art support services for their research. These will include the following: A) Genetic Linkage and Epidemiology; B) Tissue, Cell and DNA processing; C) Genotyping and Molecular Diagnostics; D) DNA Sequencing and Synthesis. These Cores will afford investigators resources that otherwise would be difficult if not impossible to access. The Cores will provide crucial underpinning for the closely liked Pilot and Feasibility (P&F) Study Program that will generate the intellectual stimulus for expanding the horizons of the SDRC by nurturing the development of new ideas that can ultimately be translated into independently funded programs. The infrastructure provided by the Cores will facilitate the advancement of four important underlying themes in research in molecular genetics, as featured in the Pilot and Feasibility Studies. These include structural biology, functional integrity of gene/protein systems, statistical analysis of datasets, and finally, translational applications of basic science research. Proposals were solicited from all Dermatology departments in New York State and from the Columbia faculty of the 12 submitted. After rigorous review, 4 were selected for inclusion in this proposal representing a healthy mix from within and outside the Department of Dermatology. The research-related Cores and P&F Studies are incorporated under the aegis of an Administrative Core that will provide organizational support and assure maximally efficient integration of the SDRC among its multiple components and within CPMC. This proposal provides a framework and a foundation for the creation of a unique resource for investigations in cutaneous biology focused on the genetic basis of skin disease, which, when leveraged to the substantial new investment already in place at CPMC, will help to assure a robust future for innovative dermatologic research in this region. The major strength of this proposal lies in the convergence of established and productive researchers with a broad range of expertise in skin disease research employing novel approaches on a focused theme.